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Shortsightedness is becoming more common. Douglas Fredrick describes recent research into this condition and discusses future management of patients
Myopia is a leading cause of loss of vision throughout the world, and its prevalence is increasing. Although most researchers agree that people's refractive status is in large part genetically determined, a growing body of evidence shows that visual experiences early in life may affect ocular growth and eventual refractive status. This review describes recent human and animal research into the pathogenesis of myopia and discusses implications for the management of patients.
This review article was prepared by searching Medline for citations of articles in English using the keyword “myopia.” In addition, abstracts from the annual meetings of the Association for Research in Vision and Ophthalmology were reviewed.
Myopia, commonly referred to as shortsightedness, is a common cause of visual disability throughout the world. The World Health Organization has grouped myopia and uncorrected refractive error with cataract, macular degeneration, infectious disease, and vitamin A deficiency among the leading causes of blindness and vision impairment in the world.1 People with myopia can be classified in two groups, those with low to modest degrees of myopia (referred to as “simple” or “school” myopia, 0 to −6 dioptres) and those with high or pathological myopia (greater than −6 dioptres). Simple myopia can be corrected with spectacles or contact lenses, whereas “high” (pathological) myopia is often associated with potentially blinding conditions such as retinal detachment, macular degeneration, and glaucoma (fig (fig11).
The prevalence of myopia varies by country and by ethnic group, reaching as high as 70-90% in some Asian populations.2,3 In Japan it is estimated that more than one million people suffer from vision impairment associated with high myopia.4 According to epidemiological evidence the prevalence of myopia is increasing, especially in Asian populations.5 The prevalence of pathological myopia is estimated at 1-3% in population based studies.6 In addition to the human cost of visual disability, there is a profound economic cost to society. In the United States, for example, the treatment of myopia costs an estimated $250m (£173m, €281m) per year.7 As the prevalence of simple myopia increases, the incidence of pathological myopia may also increase. Since no current treatments can reverse the structural changes of pathological myopia, preventing myopia has long been a goal of ophthalmologists and scientists researching vision. Understanding the mechanisms and factors that affect ocular growth is prerequisite to development of these therapeutic strategies.
To obtain clear vision, the eye must accurately focus an image in space on the retina. The main ocular determinants of refraction are the focusing power of the cornea and crystalline lens and the length of the eye. In myopia, the image is focused in front of the retina because the cornea or lens curvature is too strong or the eye is too long (axial myopia). When the optical components focus the image perfectly on the retina, this is described as emmetropia, and when the eye focuses the image behind the retina, this is described as hyperopia. Refractive error is measured in dioptres (D), and myopia is designated with a minus sign. Mild myopia is 0 D to −1.5 D, moderate −1.5 D to −6.0 D, and high myopia −6.0 D or more. Pathological myopia occurs with more than −8.0 D, although retinal disease, cataract, and glaucoma—the associated threats to vision—can also occur in patients with moderate and high myopia. At birth, most infants are hyperopic, but when the eyes grow they usually become less hyperopic and by age 5-8 years emmetropic. This process, wherein the refractive state of children's eyes shifts in magnitude and reduces in variance to reach near emmetropia, is called emmetropisation. The question for researchers is how much of this emmetropisation process is genetically determined and how much it is modulated by early visual experience, and epidemiological research into this question must be carefully conducted. Historically, most research into myopia has been limited by its retrospective nature; lack of measurement of ocular refractive variables of patient and parents; lack of adequate randomisation, control group, and follow up; and poor therapeutic compliance. In the past decade, well designed epidemiological protocols have been used to investigate the epidemiology of myopia.8
The two lines of research that support the idea that myopia and refractive errors are in large part genetically determined come from twin studies and studies of refractive errors in parents and their children. Two well conducted and well controlled studies show that refractive errors are much more strongly correlated in monozygotic twins than in dizygotic twins.9,10 A study of the correlation between refractive error in parents and siblings showed stronger correlations than would be expected by chance.11 Zadnik et al conducted perhaps the best longitudinal prospective study into refractive errors in parents and children.12 All components of refraction were measured in children, and refractive error was measured in parents. The study showed that children with myopic parents, although not yet myopic themselves, tended to have longer eyes than children with non-myopic parents, resulting in a predisposition to becoming myopic later in life. Genetic studies of families with a strong history of pathological myopia have uncovered two polymorphisms and two separate loci for high myopia, indicating an autosomal dominant predisposition for the development of pathological myopia.13,14
Additional evidence supporting the role of genetics in the development of myopia includes the wide variability of the prevalence of myopia in different ethnic groups.15 The prevalence of myopia in Asia is as high as 70-90%, in Europe and America 30-40%, and in Africa 10-20%.
People who wear spectacles for myopia may remember being told that they would ruin their eyes if they read in the dark or in a moving car or held the book too close to their faces (fig (fig2).2). The idea that the way in which we use our eyes early in life can affect ocular growth and refractive error is gaining scientific credence. It has been hypothesised that prolonged reading or the retinal blur of prolonged near work leads to the development of myopia. This is supported by evidence showing an increase in the prevalence of myopia from near 0% to rates found in the Western population in aboriginal peoples exposed to a Western curriculum of education.16 The correlation between level of academic achievement and the prevalence and progress of myopic refractive errors is strong; people whose professions entail much reading during either training or performance of the occupation (lawyers, physicians, microscopists, and editors) have higher degrees of myopia, and the myopia may progress not just in people's teenage years but throughout their 20s and 30s.3,17–20 Although it has been presumed that people with higher intelligence have higher degrees of myopia, these studies have been confounded by the higher degrees of educational attainment and cumulative amount of near work in patients with a higher IQ, and intelligence per se thus cannot be correlated strongly with myopia.
Observations by researchers that altering the visual experience of young animals can affect the growth of the eye have led to the experimental use of animals to investigate myopia. Whether using primates (monkeys, marmosets, or tree shrews) or chickens, investigators have shown that when a clear, formed image is not allowed to be focused on the retina (by suturing up eyelids or placement of translucent goggles) high myopia will develop in the eyes of young animals.21–24 The ocular growth seems to be focally controlled in birds' eyes, as hemiretinal occlusion leads to only hemiocular elongation (fig (fig3).3).
The chicken model has been used to try to characterise the possible signal that triggers retinal, choroidal, and scleral growth. Possible modulators of growth include acetylcholine, dopamine, vasoactive intestinal polypeptide, and glucagon.25 Altering the visual environment leads to changes in the synthesis of mRNA and the concentration of matrix metalloproteinase. Further elucidation of the biochemical processes in these animal models of myopia may have implications for treating myopia in humans.
Before we conclude that myopia in humans is analogous to experimentally induced myopia in animal models, we should bear in mind that naturally occurring disease processes causing deprivation of formed vision do affect human infants. In periocular haemangiomas and congenital cataracts, the two conditions that have been most studied, occlusion of the visual axis occurs in the first few months of life.26,27 In eyes that are not treated promptly, axial elongation and myopia develop. Other conditions that are associated with myopia include congenital ptosis; perinatal, vitreal, and retinal haemorrhages; and inflammatory keratitis. These naturally occurring experiments of deprivation of formed vision are consistent with the animal models previously described.
On the basis of epidemiological studies of myopia, experimental animal models of myopia, and analysis of people with visual deprivation early in life, a model of myopia development can be postulated (fig (fig4).4). Prolonged near work was thought to lead to progressive myopia through the direct physical effect of prolonged accumulation, but according to current theory prolonged near work leads to myopia via the blurred retinal image that occurs during near focus. This retinal blur initiates a biochemical process in the retina to stimulate biochemical and structural changes in the sclera and choroid that lead to axial elongation.28
People with shortsightedness have poorer ability to focus accurately by accommodation, which leads to even more retinal blur and defocus. In this model, the infant eye at birth is hyperopic or shorter than it should be in order to focus incoming light properly. Early visual experiences affect the growth of the eye. Deprivation of formed vision leads to an eye that grows in uncontrolled fashion, ever searching for a focal point, bypassing emmetropia, and developing axial myopia. People who do not have a strong predisposition for myopia—who have no family history of high myopia or who come from an ethnic group with no strong preponderance of myopia—also begin life hyperopic, and emmetropisation occurs until the images are properly focused on the retina, when the process stops. Further myopiogenic stimuli such as prolonged reading or occupations that require extensive near work may lead to mild myopia later in life.
In children with a familial or ethnic predisposition to myopia the emmetropisation process continues, but they become mildly myopic early in life (fig (fig4).4). When they are exposed to myopiogenic factors, such as extensive near work, which produces blur and defocused images on the retina, myopisation consequently proceeds unchecked, searching for a focal point, which causes axial elongation and moderate myopia in late adolescence. Additional myopiogenic factors such as extensive near work in secondary or postgraduate school or in an occupation can lead to higher degrees of myopia. This model raises the question whether any interventions should be recommended to stop or slow this abnormal process of myopisation.
Most myopic children will develop only low to moderate levels of myopia, but some will progress rapidly to high myopia. Risk factors for the development of high myopia include ethnicity, parental refraction, and rate of progession of myopia. In those children at risk, interventions should be considered.
Efforts to prevent the progression of myopia date back centuries, and eye exercises, medications, and hygiene have been proposed to prevent weak eyes. Most modern efforts have been focused on decreasing the accommodative requirements of the eyes. Anticholinergics such as atropine have been used in combination with bifocals in an attempt to slow the progression of myopia. Although progression is slowed during treatment, the long term effects seem to be a difference of no more than 1-2 dioptres, and no cases of pathological myopia have been prevented with this treatment.
Anticholinergics may act by a direct affect on the retina. Pirenzepine is a selective antimuscarinic that has no anti-accommodative effects. It has been shown to retard experimental myopia in chickens through a direct effect on the retina and sclera, and its efficacy is currently being investigated in a multicentre trial. Other biochemical modulators of scleral growth are currently being investigated in animal models, and limited human trials are under way.
Accommodative effort and retinal blur can be minimised by bifocal glasses, which change the focal point for near work. Use of bifocals may slow the rate of progression of myopia; prospective randomised trials are addressing this question.29 Rigid or gas permeable contact lenses may offer a mode of treatment that may be effective in slowing the progression of myopia.30 The rate of progression of myopia is slower in patients using these contact lenses than in patients using lenses that are placed in spectacles.31 The exact mechanism by which rigid contact lenses prevent axial myopia from developing is unclear. Laser refractive surgery can eliminate the refractive condition of myopia, but it does not decrease the rate of the blinding conditions of retinal detachment, macular degeneration, and glaucoma associated with high myopia.32
Other interventions have included the use of vitamins, scleral surgery to provide shortening of the eye, biofeedback, ocular hypotensives, ocular relaxation techniques, and acupuncture, and proponents of these treatments often make unsubstantiated and exaggerated claims of success. Their efficacy has not been confirmed in randomised controlled trials.
Until these treatments have been developed further parents of myopic children should ensure that refractive errors are corrected accurately as overcorrection may induce more myopia. Parents should consider the use of bifocal lenses to prevent retinal blur in patients with known accommodative lag and provide adequate lighting for reading and advocate a healthy balance of physical activity coupled with encouragement to enjoy the activity of reading. Doctors should encourage young shortsighted people to participate in clinical trials investigating strategies to prevent myopia.
Norton TT. Animal models of myopia: learning how vision controls the size of the eye. Inst Lab Anim Res J 1999;40:59-77.
Smith EL, Hung LF. The role of optical defocus in regulating refractive development in infant monkeys. Vis Res 1999;39:1415-35.
Goss DA, Zhai H. Clinical and laboratory investigations of the relationship of accommodation and convergence function with refractive error. A literature review. Doc Ophthalmol 1994;86:349-80.
Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) study (www.nei.nih.gov/neitrials/static/study72.htm)
Contact Lens and Myopia Progression (CLAMP) study (www.nei.nih.gov/neitrials/static/study81.htm). Study of rigid contact lenses versus spectacles on progression of myopia
Correction of Myopia Evaluation Trial (COMET) (www.nei.nih.gov/neitrials/static/study9.htm). Study of bifocals versus single vision lenses
Competing interests: DRF has done consultancy work for Novartis.